Non-Hodgkin lymphomas (NHLs) are cancers of B, T or natural killer lymphocytes. The two most common types of NHL, follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), together comprise 60% of new B-cell NHL diagnoses each year in North America [1]. FL is an indolent and typically incurable disease characterized by clinical and genetic heterogeneity. DLBCL is aggressive and likewise heterogeneous, comprising at least two distinct subtypes that respond differently to standard treatments. Both FL and the germinal centre B-cell (GCB) cell of origin (COO) subtype of DLBCL derive from germinal centre B cells whereas the activated B-cell (ABC) variety, which exhibits a more aggressive clinical course, is thought to originate from B cells that have exited, or are poised to exit, the germinal centre [2]. Current knowledge of the specific genetic events leading to DLBCL and FL is limited to the presence of a few recurrent genetic abnormalities [2]. For example, 85-90% of FL and 30-40% of GCB DLBCL cases [3, 4] harbour t(14;18)(q32;q21), which results in deregulated expression of the BCL2 oncoprotein. Other genetic abnormalities unique to GCB DLBCL include amplification of the c-REL gene and of the miR-17-92 microRNA cluster [5]. In contrast to GCB cases, 24% of ABC DLBCLs harbour structural alterations or inactivating mutations affecting PRDM1, which is involved in differentiation of GCB cells into antibody-secreting plasma cells [6]. ABC-specific mutations also affect genes regulating NF-κB signalling [7-9], with TNFAIP3 (A20) and MYD88 [10] the most abundantly mutated in 24% and 39% of cases respectively.
Despite the disparity in response to therapy of the individual subtypes and the knowledge of clear genetic differences between the subtypes, clearly identifying B-cell NHLs remains challenging. Accordingly, there is a need for improved methods of identifying as well as classifying B-cell NHLs including GCB and ABC DLBCLs.